The Udall Center for Excellence in Parkinson's Disease Research at the Mayo Clinic is an integrated, multidisciplinary center that studies the Genetics and Molecular Biology of Parkinsonism. The Center draws upon the clinical strengths of the Mayo Clinic Movement Disorder Section as well as epidemiologic and longitudinal studies of Parkinson's disease (PD), dementia with Lewy bodies and aging that provide clinical material for research projects. The Clinical Core is a multi-national effort to identify and characterize multiplex families with PD for genetic studies of PD. The Clinical Core also recruits and follows sporadic PD patients and arranges for postmortem studies. The Genetic Core provides genetic screening and performs genome wide linkage studies of familial PD. When permission is granted, samples are submitted to the NINDS DNA repository. The Neuropathology Core performs postmortem evaluations of PD, provides histologic support for projects and provides postmortem material collected through several different avenues for the research projects. Project 1 builds upon progress from the previous funding period demonstrating multiplication of the alpha-synuclein gene (SCNA) in autosomal dominant, early-onset PD and focuses on population genetics of SNCA, characterization of SNCA multiplications (including the size and genes within the multiplication regions), and measuring temporal and regional alpha-synuclein expression in normals and a-synucleinopathies. Project 2 is a clinicopathologic study that determines the frequency and clinical expression of Lewy bodies in normal individuals using the Mayo Medical Records Linkage System, with studies on the role of neuronal loss, inflammation and tau on clinical features. Project 3 uses cell lines that inducibly express alpha-synuclein as well as mitochondrial toxins, such as rotenone, to study truncated and aggregated alpha-synuclein with the goal of determining the role of interacting proteins in aggregate formation and the effects of aggregates on proteasome function and gene expression.